Cleveland Clinic, CWRU School of Medicine team discovers key mechanisms to inhibit

A team of researchers from the Cleveland Clinic and Case Western Reserve School of Medicine have identified critical complex mechanisms involved in the metastasis of deadly "triple negative" breast cancers (TNBC). These tumors are extremely difficult to treat, frequently return after remission, and are the most aggressive form of breast cancer in women. The discovery of this critical interaction of mechanisms could be used to develop new life saving treatments to kill metastatic tumors in TNBC.

"In previous findings published over the past 10 years, our teams have described key mechanisms in these critical proteins," said Khalid Sossey-Alaoui, PhD, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic. "A key component in the deadly metastatic potential of TNBC tumors is that they spread through tissues outside the breast very quickly. The two proteins that we studied, WAVE3 and TGF-β, when together, promote tumor aggressiveness."

"We found important biological implications," said William Schiemann, PhD, an associate professor, Division of General Medical Sciences-Oncology, Case Western Reserve School of Medicine, and co-leader of the Breast Cancer Program at the Case Comprehensive Cancer Center. "For the first time, we uncovered an interplay between the two proteins that can inhibit or suppress TNBC - a discovery that has the potential to inhibit proliferations of the tumor."

The next step in the research process is to find a way to deliver inhibitors to the tumor. Using nanoparticles, the Sossey-Alaoui, Schiemann team hope to deliver therapies directly to the site of the tumor and reverse the disease. Their goal is to move this basic research into clinical trials in the next three years.

"This finding helps to uncover the complex cascade of events that lead to metastasis, " said Stanton Gerson, MD, director of the Case Comprehensive Cancer Center and director of the Seidman Cancer Center at UH Case Medical Center. "These studies are part of a broad initiative in breast cancer research through numerous collaborative efforts at the Case Comprehensive Cancer Center. Using a team science approach is the most efficient and productive way to have an impact in cancer."

Metastasis is a complex, multi-stage process in which primary tumor cells invade the surrounding cells, tissues and organs, integrate into blood vessels, and survive and move throughout the body. Metastasis of primary mammary tumors accounts for the vast majority of deaths of breast cancer patients. The five-year survival rate for patients with breast cancer drops precipitously from 98% for individuals with localized disease to 23% for those with metastatic disease.

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Research support was provided in part by the National Institutes of Health to W.P.S. (CA129359) and E.F.P. (HL073311 and HL HL096062), and by the Department of Defense to K.S.-A. (BC073783) and to M.A.T.(BC093128). Additional support was provided to W.P.S. and K.S.-A. by pilot funds from the Case Comprehensive Cancer Center (P30 CA043703).

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Nine Nobel Laureates have been affiliated with the School of Medicine.

Annually, the School of Medicine trains more than 800 MD and MD/PhD students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."

The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. http://casemed.case.edu

About Case Comprehensive Cancer Center

Case Comprehensive Cancer Center is an NCI-designated Comprehensive Cancer Center located at Case Western Reserve University. The center, now in its 25th year of funding, integrates the cancer research activities of the largest biomedical research and health care institutions in Ohio - Case Western Reserve, University Hospitals (UH) Case Medical Center and the Cleveland Clinic. NCI-designated cancer centers are characterized by scientific excellence and the capability to integrate a diversity of research approaches to focus on the problem of cancer. It is led by Stanton Gerson, MD, Asa and Patricia Shiverick- Jane Shiverick (Tripp) Professor of Hematological Oncology, director of the National Center for Regenerative Medicine, Case Western Reserve, and director of the Seidman Cancer Center at UH Case Medical Center.

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